Constructing calendars in the brain.

By studying an enigmatic condition called, "calendar synesthesia", we explored the elusive boundary between perception, visual imagery, and the manner in which we construct an internal mental calendar by mapping time-sequences onto spatial maps. We use a series of demonstrations to establish that these calendars act more like real objects activating sensory pathways rather than purely abstract symbolic descriptions that bear no resemblance to an actual calendar. We propose that the calendar is enshrined in acircuitry involving the hippocampal place-cells and entorhinal grid-cells, which are connected to the angular gyrus (involved with computing sequences) via the inferior longitudinal fasciculus.

Synesthetic colors induced by graphemes that have not been consciously perceived.

Grapheme-color synesthetes experience colors when they see printed letters of the alphabet. Currently, we tested four "projector" synesthetes, whose colors evoked by graphemes have sensory support or quale and appear to be restricted spatially to the letters like real colors. We use three different kinds of puzzle pictures that contained hidden letters, which require 30 s or more for nonsynesthetes to identify. Grapheme-color projector synesthetes recognize them three times faster and report that the colors were evoked before conscious letter recognition, clueing them as to what the letters were. Subjectively, the synesthetic subjects reported that they also saw mirror-reversed letters in the same colors as nonreversed letters which enabled them to read mirror-reversed text at thrice the normal speed. We conclude that in some synesthetes colors are evoked preconsciously early in sensory processing.

Primary somatosensory cortex hand representation dynamically modulated by motor output.

The brain's primary motor and primary somatosensory cortices are generally viewed as functionally distinct entities. Here we show by means of magnetoencephalography with a phantom-limb patient, that movement of the phantom hand leads to a change in the response of the primary somatosensory cortex to tactile stimulation. This change correlates with the described conscious perception and suggests a greater degree of functional unification between the primary motor and somatosensory cortices than is currently realized. We suggest that this may reflect the evolution of this part of the human brain, which is thought to have occurred from an undifferentiated sensorimotor cortex.

External self-representations improve self-awareness in a child with autism.

We have previously suggested that the social symptoms of autism spectrum disorder (ASD) could be caused in part by a dysfunctional mirror neuron system (MNS). Since the recursive activity of a functioning MNS might enable the brain to integrate visual and motor sensations into a coherent body schema, the deficits in self-awareness often seen in ASD might be caused by the same mirror neuron dysfunction. CL is an autistic adolescent who is profoundly fascinated with his reflection, looking in mirrors at every opportunity. We demonstrate that CL's abnormal gait improves significantly when using a mirror for visual feedback. We also show that both the fascination and the happiness that CL derives from looking at a computer-generated reflection diminish when a delay is introduced between the camera input and screen output. We believe that immediate, real-time visual feedback allows CL to integrate motor sensations with external visual ones into a coherent body schema that he cannot internally generate, perhaps due to a dysfunctional MNS.

Survival of the synesthesia gene: why do people hear colors and taste words?

Synesthesia is a perceptual experience in which stimuli presented through one modality will spontaneously evoke sensations in an unrelated modality. The condition occurs from increased communication between sensory regions and is involuntary, automatic, and stable over time. While synesthesia can occur in response to drugs, sensory deprivation, or brain damage, research has largely focused on heritable variants comprising roughly 4% of the general population. Genetic research on synesthesia suggests the phenomenon is heterogeneous and polygenetic, yet it remains unclear whether synesthesia ever provided a selective advantage or is merely a byproduct of some other useful selected trait. Progress in uncovering the genetic basis of synesthesia will help us understand why synesthesia has been conserved in the population.

Parietal connectivity mediates multisensory facilitation.

Our senses interact in daily life through multisensory integration, facilitating perceptual processes and behavioral responses. The neural mechanisms proposed to underlie this multisensory facilitation include anatomical connections directly linking early sensory areas, indirect connections to higher-order multisensory regions, as well as thalamic connections. Here we examine the relationship between white matter connectivity, as assessed with diffusion tensor imaging, and individual differences in multisensory facilitation and provide the first demonstration of a relationship between anatomical connectivity and multisensory processing in typically developed individuals. Using a whole-brain analysis and contrasting anatomical models of multisensory processing we found that increased connectivity between parietal regions and early sensory areas was associated with the facilitation of reaction times to multisensory (auditory-visual) stimuli. Furthermore, building on prior animal work suggesting the involvement of the superior colliculus in this process, using probabilistic tractography we determined that the strongest cortical projection area connected with the superior colliculus includes the region of connectivity implicated in our independent whole-brain analysis.

Enhanced mental rotation ability in time-space synesthesia.

Time-space synesthesia is a variant of sequence-space synesthesia and involves the involuntary association of months of the year with 2D and 3D spatial forms, such as arcs, circles, and ellipses. Previous studies have revealed conflicting results regarding the association between time-space synesthesia and enhanced spatial processing ability. Here, we tested 15 time-space synesthetes, and 15 non-synesthetic controls matched for age, education, and gender on standard tests of mental rotation ability, spatial working memory, and verbal working memory. Synesthetes performed better than controls on our test of mental rotation, but similarly to controls on tests of spatial and verbal working memory. Results support a dissociation between visuo-spatial imagery and spatial working memory capacity, and suggest time-space synesthesia is associated only with enhanced visuo-spatial imagery. These data are consistent with the time-space connectivity thesis that time-space synesthesia results from enhanced connectivity in the parietal lobe between regions supporting the representation of temporal sequences and those underlying visuo-spatial imagery.

The appearance of new phantom fingers post-amputation in a phocomelus.

We report the unusual case of a woman with right upper limb phocomelia who, post-amputation of her right hand following trauma, sprouted a phantom hand that contained five digits, including a phantom thumb and index finger that had been absent since her birth. These two phantom digits were initially half normal size, however, more than three decades later, with mirror visual feedback treatment, she was able to elongate them to normal length. This suggests that a hardwired representation of a complete hand had always been present in her brain, but inhibited by the presence of afferents from the phocomelic hand. Amputation of the phocomelic hand then led to disinhibition of this dormant representation, and the emergence of a phantom hand with five fingers, which was then further enhanced by false visual feedback from a mirror. The case powerfully demonstrates the interaction of nature and nurture in creating and sustaining body image.

Xenomelia: a new right parietal lobe syndrome.

BACKGROUND: Damage to the right parietal lobe has long been associated with various disorders of body image. The authors have recently suggested that an unusual behavioural condition in which otherwise rational individuals desire the amputation of a healthy limb might also arise from right parietal dysfunction. METHODS: Four subjects who desired the amputation of healthy legs (two right, one left and one, at first, bilateral and then left only) were recruited and underwent magnetoencephalography (MEG) scans during tactile stimulation of sites above and below the desired amputation line. Regions of interest (ROIs) in each hemisphere (superior parietal lobule (SPL), inferior parietal lobule, S1, M1, insula, premotor cortex and precuneus) were defined using FreeSurfer software. RESULTS: Analysis of average MEG activity across the 40-140 ms post-stimulation timeframe was carried out using an unpaired t test. This revealed significantly reduced activation only in the right SPL ROI for the subjects' affected legs when compared with both subjects' unaffected legs and that of controls. CONCLUSIONS: The right SPL is a cortical area that appears ideally placed to unify disparate sensory inputs to create a coherent sense of having a body. The authors propose that inadequate activation of the right SPL leads to the unnatural situation in which the sufferers can feel the limb in question being touched without it actually incorporating into their body image, with a resulting desire for amputation. The authors introduce the term 'xenomelia' as a more appropriate name than apotemnophilia or body integrity identity disorder, for what appears to be an unrecognised right parietal lobe syndrome.

Magnetoencephalography reveals early activation of V4 in grapheme-color synesthesia.

Grapheme-color synesthesia is a neurological phenomenon in which letters and numbers (graphemes) consistently evoke particular colors (e.g. A may be experienced as red). The cross-activation theory proposes that synesthesia arises as a result of cross-activation between posterior temporal grapheme areas (PTGA) and color processing area V4, while the disinhibited feedback theory proposes that synesthesia arises from disinhibition of pre-existing feedback connections. Here we used magnetoencephalography (MEG) to test whether V4 and PTGA activate nearly simultaneously, as predicted by the cross-activation theory, or whether V4 activation occurs only after the initial stages of grapheme processing, as predicted by the disinhibited feedback theory. Using our high-resolution MEG source imaging technique (VESTAL), PTGA and V4 regions of interest (ROIs) were separately defined, and activity in response to the presentation of achromatic graphemes was measured. Activation levels in PTGA did not significantly differ between synesthetes and controls (suggesting similar grapheme processing mechanisms), whereas activation in V4 was significantly greater in synesthetes. In synesthetes, PTGA activation exceeded baseline levels beginning 105-109ms, and V4 activation did so 5ms later, suggesting nearly simultaneous activation of these areas. Results are discussed in the context of an updated version of the cross-activation model, the cascaded cross-tuning model of grapheme-color synesthesia.

The use of visual feedback, in particular mirror visual feedback, in restoring brain function.

This article reviews the potential use of visual feedback, focusing on mirror visual feedback, introduced over 15 years ago, for the treatment of many chronic neurological disorders that have long been regarded as intractable such as phantom pain, hemiparesis from stroke and complex regional pain syndrome. Apart from its clinical importance, mirror visual feedback paves the way for a paradigm shift in the way we approach neurological disorders. Instead of resulting entirely from irreversible damage to specialized brain modules, some of them may arise from short-term functional shifts that are potentially reversible. If so, relatively simple therapies can be devised--of which mirror visual feedback is an example--to restore function.

Visual field heterogeneity, laterality, and eidetic imagery in synesthesia.

JS was a grapheme-color synesthete in whom numerals and letters of the alphabet consistently evoked colors. In the first set of experiments we showed that the color - in a consistent and reliable manner - was most pronounced in the left visual field and in central vision. In the second experiment we devised a novel test for eidetic imagery and showed that his self-report of enhanced imagery could be verified experimentally. The implications of these findings for the level at which synesthesia occurs, the 'enhanced cross-activation' model, and the mechanisms of visual memory are discussed.

Temporal sequences, synesthetic mappings, and cultural biases: the geography of time.

Time-space synesthetes report that they experience the months of the year as having a spatial layout. In Study 1, we characterize the phenomenology of calendar sequences produced by synesthetes and non-synesthetes, and show a conservative estimate of time-space synesthesia at 2.2% of the population. We demonstrate that synesthetes most commonly experience the months in a circular path, while non-synesthetes default to linear rows or rectangles. Study 2 compared synesthetes' and non-synesthetes' ability to memorize a novel spatial calendar, and revealed better performance in synesthetes. The capacity to learn mappings between arbitrary spatial forms and temporal sequences is present in all individuals, and time-space synesthetes' enhanced visuo-spatial memory abilities may underlie their creation of idiosyncratic spatial calendar forms.

Neurocognitive mechanisms of synesthesia.

Synesthesia is a condition in which stimulation of one sensory modality causes unusual experiences in a second, unstimulated modality. Although long treated as a curiosity, recent research with a combination of phenomenological, behavioral, and neuroimaging methods has begun to identify the cognitive and neural basis of synesthesia. Here, we review this literature with an emphasis on grapheme-color synesthesia, in which viewing letters and numbers induces the perception of colors. We discuss both the substantial progress that has been made in the past fifteen years and some open questions. In particular, we focus on debates in the field relating to the neural basis of synesthesia, including the relationship between synesthesia and attention and the role of meaning in synesthetic colors. We propose that some, but probably not all, of these differences can be accounted for by differences in the synesthetes studied and discuss some methodological implications of these individual differences.

Post-stroke tactile allodynia and its modulation by vestibular stimulation: a MEG case study.

BACKGROUND: There is behavioural evidence that caloric vestibular stimulation (CVS) can alleviate central pain. Several such patients have also noted that it reduces tactile allodynia, an especially ill-understood phenomenon in these patients. AIMS OF THE STUDY: The first aim is to use magnetoencephalography (MEG) to study neural activity associated with tactile allodynia in central post-stroke pain (CPSP). The second is to assess how this would be affected, if at all, by CVS. The third is to assess the ability of the VESTAL solution for MEG to detect anterior cingulate activation. METHODS: A 58-year-old woman with CPSP, and marked unilateral tactile allodynia, participated in a MEG study with imaging pre- and post-CVS. RESULTS: Tactile simulation within the patient's allodynic area resulted in contralateral activation of the primary motor and anterior cingulate cortices, which had normalized 24 h post-CVS. CONCLUSIONS: We suggest that the unexpected primary motor cortex activation in response to light touch in the allodynic area arises from inappropriate activation of a normal mechanism, which may occur when a threat to homeostasis is present, to lower motor thresholds and allow for more rapid performance of corrective actions. We propose this may be mediated by the interoceptive cortex in the dorsal posterior insula.

Size reduction using Mirror Visual Feedback (MVF) reduces phantom pain.

Following limb amputation patients continue to feel the vivid presence of a phantom limb. A majority of patients also experience pain in the phantom and sometimes (as in our case DS) the pain is severe. Remarkably we find that optically 'resurrecting' the phantom with a mirror and using a lens to make the phantom appear to shrink caused the pain to 'shrink' as well.

Behavioural evidence for vestibular stimulation as a treatment for central post-stroke pain.

BACKGROUND: Central post-stroke pain (CPSP) is often resistant to treatment. We have previously proposed that caloric vestibular stimulation might alleviate it. METHODS: We conducted a single blind placebo controlled investigational study of caloric vestibular stimulation (CVS) in nine patients with CPSP. Participants rated their pain levels before and after the procedure on a 10 point scale. RESULTS: We found a significant immediate treatment effect of the cold water caloric stimulation with an average pain reduction of 2.58 points (SEM 0.52) for the experimental condition compared with 0.54 points (SEM 0.49) for the placebo conditions. CONCLUSIONS: Participants who responded best to CVS had suffered strokes that spared and permitted activation of the dominant parieto-insular vestibular cortex (PIVC), which is known to be located in the non-dominant hemisphere. These findings tie in closely with the thermosensory disinhibition hypothesis for central pain, which leads us to propose that vestibular stimulation may alleviate CPSP from cross activation between the PIVC and the thermosensory cortex in the adjacent dorsal posterior insula. Alternatively, if one views vestibular function and thermoregulation as part of a larger interoceptive system that exists to maintain homeostasis, then it is possible they share a common integrative mechanism in the brainstem, which may act to reset the balance in central pain.

Tactile-emotion synesthesia.

We discuss experiments on two individuals in whom specific textures (e.g., denim, wax, sandpaper, silk, etc.) evoked equally distinct emotions (e.g., depression, embarrassment, relief, and contentment, respectively). The test/retest consistency after 8 months was 100%. A video camera recorded subjects' facial expressions and skin conductance responses (SCR) were monitored as they palpated different textures. Evaluators' ratings significantly correlated with the valence of synesthetes' subjective reports, and SCR was significantly enhanced for negative synesthetic emotions. We suggest this effect arises from increased cross-activation between somatosensory cortex and insula for 'basic' emotions and fronto-limbic hyperactivation for more subtle emotions. It may represent an enhancement of pre-existing evolutionarily primitive interactions between touch and emotions.

Can vestibular caloric stimulation be used to treat apotemnophilia?

Apotemnophilia, or body integrity image disorder (BIID), is characterised by a feeling of mismatch between the internal feeling of how one's body should be and the physical reality of how it actually is. Patients with this condition have an often overwhelming desire for an amputation- of a specific limb at a specific level. Such patients are not psychotic or delusional, however, they do express an inexplicable emotional abhorrence to the limb they wish removed. It is also known that such patients show a left-sided preponderance for their desired amputation. Often they take drastic action to be rid of the offending limb. Given the left-sided bias, emotional rejection and specificity of desired amputation, we suggest that there are clear similarities to be drawn between BIID and somatoparaphrenia. In this rare condition, which follows a right parietal stroke, the patient rejects (usually) his left arm as "alien". We go on to hypothesis that a dysfunction of the right parietal lobe is also the cause of BIID. We suggest that this leads to an uncoupling of the construct of one's body image in the right parietal lobe from how one's body physically is. This hypothesis would be amenable to testing by response to cold-water vestibular caloric stimulation, which is known to temporarily treat somatoparaphrenia. It could also be investigated using functional brain imaging and skin conductance response. If correct our hypothesis not only suggests why BIID arises, but also, in caloric stimulation a therapeutic avenue for this chronic and essentially untreatable condition.

Occurrence of phantom genitalia after gender reassignment surgery.

Transsexuals are individuals who identify as a member of the gender opposite to that which they are born. Many transsexuals report that they have always had a feeling of a mismatch between their inner gender-based "body image" and that of their body's actual physical form. Often transsexuals undergo gender reassignment surgery to convert their bodies to the sex they feel they should have been born. The vivid sensation of still having a limb although it has been amputated, a phantom limb, was first described by Weir Mitchell over a century ago. The same phenomenon is also occurs after amputation of the penis or a breast. Around 60% of men who have had to have their penis amputated for cancer will experience a phantom penis. It has recently been shown that a significant factor in these phantom sensations is "cross-activation" between the de-afferented cortex and surrounding areas. Despite this it also known that much of our body image is innately "hard-wired" into our brains; congenitally limbless patients can still experience phantom sensations. We hypothesise that, perhaps due to a dissociation during embryological development, the brains of transsexuals are "hard-wired" in manner, which is opposite to that of their biological sex. We go on to predict that male-to-female transsexuals will be much less likely to experience a phantom penis than a "normal" man who has had his penis amputated for another reason. The same will be true of female-to-male transsexuals who have had breast removal surgery. We also predict that some female-to-male transsexuals will have a phantom penis even although there is not one physically there. We believe that this is an easily testable hypothesis, which, if correct, would offer insights into both the basis of transsexuality and provide farther evidence that we have a gender specific body image, with a strong innate component that is "hard-wired" into our brains. This would furnish us with a better understanding the mechanism by which nature and nurture interact to link the brain-based internal body image with external sexual morphology. We would emphasise here that transsexuality should not be regarded as "abnormal" but instead as part of the spectrum of human behaviour.